Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.

Aim: There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Methods: Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. Results: At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Conclusions: Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

Small cell carcinoma esophagus-A tertiary cancer center experience of a rare variant.

BACKGROUND: Esophageal cancer is quite prevalent worldwide and usually carries a poor prognosis. Histologically, although squamous cell carcinoma and adenocarcinoma predominate, small cell carcinoma (SmCC) cases have been reported. Overall, there is a paucity of literature regarding this variant. In this article, we aim to highlight this uncommon entity of carcinoma esophagus and share our experience of SmCC patients seen over a decade at our institute. METHOD: Records of patients with SmCC histology from 2010 to 2020 were assessed. Patients' demographic characteristics, clinical characteristics, treatment received, and outcomes were taken into consideration. Results were analyzed statistically using SPSS version 22. RESULTS: Fourteen patients (nine males and five females) with a median age of 57 years (range: 35 - 72 years) were analyzed. The majority of the patients 10/14 (71.4%) received palliative radiotherapy of either 30Gy/10 fractions or 35Gy/15 fractions. Only 1/14 (7.14%) patients received neoadjuvant chemotherapy and concurrent chemoradiation (CCRT). Overall, partial response was noted in all 11 patients (78.6%) who received treatment. The average median survival was 5 months (range: 1-11 months). CONCLUSION: Although the small sample size of the study prevents us from drawing a firm conclusion, we propose national and international collaborative prospective studies for framing definitive oncologic management strategies for this rare histological variant of esophageal cancer.

Role of external radiation in benign tumors: A clinical outcome and safety audit of 7 years from a tertiary care center in India.

PURPOSE: Radiotherapy (RT) is a well-established modality for treating malignancies, but its role in treatment of benign lesions has not been well explored. Herein, we present a retrospective analysis of a 7-year data regarding the benefit and the safety profile of RT for treating benign tumors in our institute. MATERIALS AND METHODS: Data of 23 patients who received RT for benign tumors from January 2015 to April 2022 were retrieved, and a retrospective analysis was conducted. All the pertinent demographic data, treatment and follow-up data were retrieved. The most common presentations were nasopharyngeal angiofibroma, vertebral hemangioma, paraganglioma, and others. The most common sites of occurrence were head and neck (43%) and paravertebral region (22%). Volumetric modulated arc therapy was the most commonly employed RT technique (39%), followed by three-dimensional conformal RT (34%) and two-dimensional conventional radiotherapy (26%). The median RT dose delivered was 36 Gy (range: 20-54 Gy). RESULTS: The median follow-up duration was 53 months (range: 3-120 months). Nine (39%) patients had progressive disease with a median time to progression of 8 months (range: 1-30 months). The median disease-free survival (DFS) was 70 months, while the 1-, 3-, and 5-year DFS rates were 97%, 88%, and 62%, respectively. Four patients (17%) died, all due to disease progression. The 1-, 3-, and 5-year overall survival rates was 97%, 85%, and 50%, respectively. The rate of radiation-induced cancer (RIC) was 0% as none of the patients had developed RIC secondary to radiation. CONCLUSION: RT is a safe and an effective option to manage benign tumors either in an adjuvant setting or in inoperable patients requiring definitive treatment, as well as in a setting to alleviate symptoms, providing excellent survival benefits. However, further prospective studies with much higher sample size are required to establish the absolute benefit and to estimate the risk of RIC, which will further direct for a better utilization of RT in treating benign tumors.

Assessment of Shame and Stigma in Head and Neck Cancer: A Meta-Analysis.

Background: Head and neck cancer is the most common cancer around the globe, following lung cancer and breast cancer. Treatment at advanced stages of head and neck cancer is usually followed intense surgical procedures, which leads to mutilation among patients. Mutilation imparts a sense of disgrace and causes a feeling of shame and stigma in the patient. The feeling of shame and stigma persists over time and affects the overall long-term survival of patients by deteriorating their quality of life. Objectives: Since shame and stigma is an important psychological domain of head and neck cancer, the present article aims toward evaluating the studies published so far for the assessment of shame and stigma in head and neck cancer and highlighting the lacunae in the existing research designs. The present study also aims to design a checklist that could be followed while developing, translating, or validating a psychometric instrument that aims to measure shame and stigma in head and neck cancer. Methods: In the present metanalysis, all articles published in the past years on shame and stigma in head and neck cancer was compiled using a predefined data extraction matrix. The available literature was compiled for major objectives of the study, the sample size used, major findings, and critical lacunae that need to be addressed. Results: Shame and stigma is a very important domain of psychological well-being in head and neck cancer patients, which yet not appropriately addressed and further need to be researched. Conclusion: Future studies could be based on the lacunae highlighted in the existing literature, and the prescribed methodology checklist could be taken into consideration while conducting further studies involving developing, translating, or validating a psychometric instrument related to shame and stigma in the head and neck cancer.

Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches.

Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.

Simultaneous Integrated Boost (SIB) Versus Sequential Boost in Anal Cancer Patients: A Single-Center Experience.

PURPOSE: Concurrent chemoradiation is the standard of care for the treatment of anal cancer. Radiation can be delivered by sequential or simultaneous integrated boost (SIB) approach. The present study was conducted to compare the treatment outcomes and toxicity profile of patients with anal cancer treated with sequential boost and SIB approach. METHODS: A single-institution retrospective analysis of patients with squamous cell carcinoma of the anal canal treated between 2019 and 2022 with radical chemoradiation was performed. The sequential boost schedule consisted of 45 Gy in 25 fractions (1.8 Gy daily) to the gross tumor, nodes, and elective nodal volume, followed by a 9 Gy in five fractions boost to the gross disease. Patients receiving SIB were treated as per RTOG 0529 protocol. In both the groups, patients were treated with volumetric modulated arc therapy (VMAT). The two groups were compared in terms of overall survival (OS), colostomy-free survival (CFS), relapse-free survival (RFS), and acute toxicity profile. p-values < 0.05 were considered statistically significant. RESULTS: The patient and disease characteristics in both treatment arms were comparable. The only difference was a significantly longer overall treatment time of ≥ 50 days in the sequential arm (77.8% vs 43.8%, p = 0.04). The median follow-up was 18 months. The 2-year CFS was 80% in sequential vs 87.5% at 2 years for the SIB arm, 2-year OS 83.3% vs 58.6%, and 2-year RFS was 38.9% vs 41.7%, respectively. A total of 14 (77.8%) in sequential and 8 (50%) in the SIB arm had disease relapse. On univariate analysis, the involved pelvic lymph node significantly affected OS (HR 10.45, p = 0.03) while inguinal lymph node involvement adversely affected RFS (HR 6.16, p = 0.02). The most common acute toxicity was radiation-induced dermatitis, 15 (83.4%; 5 grade II, 10 grade III) in sequential vs 7 (43.8%; 3 each grade II and III) in the SIB group followed by hematological (61.1% vs 68.75%). However, the incidence of overall acute toxicities was significantly less in the SIB arm (p = 0.006). CONCLUSION: Our study showed that concurrent chemoradiation with the SIB-VMAT approach is well tolerated in patients of anal carcinoma and resulted in lesser treatment interruptions and comparable outcomes as compared to the sequential approach. Our results warrant further evaluation in a prospective study.

Role of Computed Tomography Perfusion in Patients with Liver Cirrhosis and Hepatocellular Carcinoma.

Background: There is a lack of data on computed tomography (CT) perfusion parameters in patients with cirrhosis and the vascular changes that occur with increasing severity of cirrhosis, as well as changes that can occur in the remote/background liver parenchyma when hepatocellular carcinoma (HCC) develops. This study aimed to evaluate the association between CT perfusion parameters in the background liver parenchyma in cirrhotic patients with and without HCC. Methods: This prospective study comprised consecutive patients with cirrhosis with or without HCC. A CT perfusion scan of the whole liver was done on a 128-detector row CT scanner in the four-dimensional spiral mode. Arterial liver perfusion (ALP), portal venous perfusion (PVP), hepatic perfusion index (HPI), blood flow (BF), blood volume (BV), and time to peak (TTP) were assessed. The perfusion parameters of the background liver parenchyma (bALP, bPVP, bHPI, bBF, bBV, and bTTP) were compared between the patients with cirrhosis (group I) and cirrhosis with HCC (group II). Perfusion parameters were also compared between the background liver parenchyma and the HCC in group II. Results: Of the 93 patients evaluated during the study period, 60 patients (30 in group I and 30 in group II, mean age, 54.5 years, 53 men) were included in the analysis. Among the perfusion parameters in the background parenchyma, bPVP was lower and bHPI was higher in group II, suggesting increased hepatic arterial perfusion of even the remote background liver parenchyma in patients with HCC (P = 0.001 and P = 0.01, respectively). Perfusion parameters were significantly altered with increasing severity of cirrhosis (based on Child-Pugh class) both within and between groups. Additionally, there were significant differences in all the perfusion parameters between HCC and the background cirrhotic liver. Conclusion: HPI and PVP of background liver parenchyma were significantly different in cirrhosis with and without HCC and also showed a worsening trend with increasing grades of cirrhosis.

Profile of 193 pediatric cancer patients managed with radiation therapy: Challenges and lessons learned.

Background: Series on radiotherapy (RT) practice in pediatric malignancies are limited in India as only a few centers practice pediatric RT, particularly under anesthesia. We aimed to study the clinical profile of pediatric cancer patients treated with RT and to analyze various challenges in pediatric RT under anesthesia. Materials and Methods: The data were prospectively maintained in Microsoft Excel spreadsheets. Pediatric cancer patients aged 0-14 years, registered in the RT department between February 1, 2019 and July 30, 2021were analyzed. Results: A total of 193 pediatric cancer patients (noncentral nervous system) received RT during the said period. Median age at presentation was 5.2 years (range: 9 months to 14 years) with a male-to-female ratio of 1.8:1. The majority of the patients were in the age group of 0-4 years (52.8%) followed by 5-9 years (29.5%) and ≥10 years (17.6%). Most common indications for RT included bone and soft-tissue tumors, retinoblastoma, Wilms tumor, neuroblastoma, and hematological malignancies. One hundred and seventy-nine (92.7%) patients received RT with curative intent, while 14 (7.3%) patients received palliative RT. Thirty (15.5%) patients needed anesthesia for RT. Ten (5.18%) patients required RT interruption due to toxicities with a median gap of 3 days. Conclusions: RT is challenging yet an important aspect of multidisciplinary care in paediatric cancers. Estimating the burden of pediatric patients in the RT department may help in assessing unmet needs, resource development, and prioritization, which may improve the cure rates.

Primary retroperitoneal squamous cell carcinoma: a literature review.

PURPOSE: Retroperitoneal squamous cell carcinoma is an extremely rare histological variant of retroperitoneal tumors. The exact etiology and origin of the same is still unknown. To date, only a few case reports have been published in the literature. Due to rarity, standard treatment protocol is not available. The article aims to review the literature and treatment options available for this uncommon entity, based on available data. METHODS: We searched the databases like PubMed, PubMed Central, Scopus, and Google Scholar with the keywords "Squamous cell carcinoma" and "retroperitoneal tumors". Peer-reviewed and recent articles were screened. RESULTS: Seven relevant articles comprising 14 cases were found. Due to the small number of reports, tabulation of treatment details and outcome was done. Like the sarcoma variant, these tumors also present with a large mass in the abdomen and abdominal discomfort. Association with human papillomavirus appears to be the most common factor that gives rise to squamous histology. CONCLUSION: Retroperitoneal SCC is an uncommonly diagnosed entity. Although no specific treatment guidelines exist for this uncommon malignancy; surgery followed by adjuvant or definitive radiotherapy with concurrent chemotherapy (in inoperable cases) seems a feasible option. Multicentre trials should be conducted for establishing definitive treatment strategies for this ailment.

Accuracy of a self-reported Measure in Psychological Assessment when the Instrument is self-administered by the Patient or when Administrated by the Clinician.

Background: Self-reported measures are the questionnaire-based instrument that are routinely used in the clinical scenario to assess psychological health. Technically, the self-reported measure should be administrated by the patients themselves but due to the complexity of tools and illiteracy among patients, clinicians often tend to interview the patients. Objective: Present article aims to compare the accuracy of a self-reported measure in the assessment of the psychological health of a patient when the instrument is self-administrated by the patient and when administrated by the clinician or researcher. Methods: We have recruited 43 patients of oral cancer in the study who have a tumor in the buccal mucosa region. The Hindi version of the shame and stigma scale was used to analyse the shame and stigma in patients. The questionnaire was first provided to the patient for the self-administration and after that clinician administrated the questionnaire to the patient by keeping the clinician blinded to the patient self-administrated responses. Results: There was no significant difference in the global mean score and mean score of various subdomains of shame and stigma scale in the self-administered and clinician-administered mode of interview. However, the clinician-administered mode could provide more accurate measures as it helps the patient towards a better understanding of questions. Conclusion: It is recommended that the newly developed or translated self-reported measure should be tested for both patient administrated and clinician administrated compatibility. Questionnaires could be administrated by the clinician in the case when the patient is illiterate or in the case when the patient does not understand the language of the instrument.

Early endometrial carcinoma: Experience and outcomes.

Aim: Endometrial carcinoma (EC) data from India are very sparse. We did a retrospective analysis of our patients registered at this peripheral cancer center based in rural Punjab and studied their outcome. Materials and Methods: Ninety-eight Stage I and II EC patients with endometroid histology registered at our institute from January 2015 to April 2020 were studied for demography, histopathology, treatment received, and outcomes. FIGO 2009 staging and new European Society for Medical Oncology (ESMO) risk group classification was used. Results: Our patients had a median age of 60 years (range 32-93 years). There were 39 (39.8%), 41 (42.0%), 4 (4.1%), 12 (12.2%) patients in the low risk, intermediate risk (IR), high intermediate risk, and high risk groups, respectively, as per new ESMO risk classification. Two (2.0%) patients had incomplete information to assign them to a particular risk group. Fifty (46.7%) patients underwent complete surgical staging and 54 (50.5%) patients received adjuvant RT. With a median follow-up of 27.0 months, there were 1 locoregional and 2 distant recurrences. There were 8 deaths in total. Three-year overall survival for the entire group is 90.6%. Conclusions: The risk group determines adjuvant treatment in endometrial cancer. Patients operated at dedicated cancer center tend to have better surgical staging and thus better outcome because of better risk stratification and grouping for adjuvant therapy. IR histology was more common in our group of patients, which is variable as compared to available literature.

Treatment outcomes of adjuvant radiotherapy in adrenocortical carcinoma - A 13-years experience from a tertiary care centre.

Purpose: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant neoplasm, usually diagnosed in advanced stage. Role and efficacy of adjuvant radiotherapy has not been well defined. The objective of this study is to describe the various clinical characteristics and prognostic factors affecting the survival of ACC along with the role radiotherapy on overall survival and relapse free survival. Methods: A retrospective analysis of 30 patients registered between 2007 and 2019 was carried out. The medical records containing clinical and treatment details were analysed. Data was analysed using SPSS 25.0. Survival curves were computed using Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic factors affecting the outcome. A p value of less than 0.05 was considered to be statistically significant. Results: The median age of patients was 37.5 years (range, 5-72 years). 20 patients were females. Twenty-six patients had advanced stage (III/IV) disease while only four patients presented in early stage. Twenty-six patients underwent total adrenalectomy. Eighty three percent patients received adjuvant radiation therapy. The median follow up was 35.5 months (range, 7 monthss-132months). The estimated three- and 5-years overall survival (OS) was 67.2% and 23.3%, respectively. Capsular invasion and positive margins were the independent prognostic factors influencing both OS and relapse free survival (RFS). Out of 25 patients who received adjuvant radiation, only three patients had local relapse. Conclusion: ACC is a rare and aggressive neoplasm with majority of patients presenting in advanced stage. Surgical resection with negative margins remains the mainstay of treatment. Capsular invasion and positive margins are independent prognostic factors for survival. Adjuvant radiation reduces the risk of local relapse and is well tolerated. Radiation can be used effectively in adjuvant and palliative settings in ACC.

Malignant Peripheral Nerve Sheath Tumor Arising from Small Bowel Mesentery: an Extremely Rare Case with Review of Literature.

PURPOSE: Malignant peripheral nerve sheath tumor (MPNST) of small bowel mesentery is a rare tumor. We report a rare case of MPNST of small bowel mesentery in a patient without neurofibromatosis (NF). METHODS: A 50-year-old male, with no features suggestive of NF1, presented to us with complaints of pain abdomen. Contrast-enhanced computed tomography (CECT) of the abdomen revealed a mass in the infrarenal region. On laparotomy, mass was seen to be arising from the mesentery of the jejunum. En-bloc resection of the tumor was done, and histopathological examination was suggestive of malignant peripheral nerve sheath tumor of the small bowel mesentery. RESULT: Patient received adjuvant external beam radiotherapy to a dose of 50.4 Gy to the tumor bed. The patient was planned for chemotherapy but absconded and later came with recurrence. The patient finally succumbed to disease. CONCLUSION: Surgery is the mainstay of treatment. Adjuvant treatment should be based on histopathological report.

Vesicovaginal Fistula Repair by Transvaginal Route: Comparison of Resource Utilisation and Outcome with Literature Reported Population Matched Cohort of Patients Operated by Minimally Invasive Route.

Introduction and Objectives: VVF is conventionally repaired by open transvaginal or transabdominal routes. In last few decades, minimally invasive techniques (laparoscopic/robotic) for VVF repair have gained popularity. We have reported our experience of transvaginal vesicovaginal fistula (VVF) repair and compared it with the literature reported population matched cohort of VVF repair done by laparoscopic or robot-assisted techniques. Material and Methods: Intraoperative and post-operative parameters including aetiology of fistula, location, operative time, blood loss, major complications, hospital stay and success rate of 202 patients with simple VVF undergoing transvaginal repair at a tertiary care hospital from 1999 to 2019 were recorded. We also compared our transvaginal repair cohort (n = 202) with the literature reported cohort of 260 patients undergoing VVF repair by minimally invasive (laparoscopic and robot assisted) techniques in the systematic review by Miklos et al. Results: Most common aetiology of VVF in our series was post hysterectomy in 122 (60.39%) cases followed by trauma during emergency caesareans section in 80 (39.60%) cases. Transvaginal route had higher success rate than minimally invasive approach (99.50 vs. 96.50%, respectively). Mean operative time was lesser in transvaginal group than the minimally invasive group (63 ± 16 min vs. 161.56 ± 41.02 min, p < 0.01) with shorter mean hospital stay in transvaginal group (3 ± 1 days vs. 3.5 ± 1.16 days, respectively, p < 0.01). Mean estimated blood loss was significantly lesser in transvaginal repair (p < 0.01). 62% patients were sexually active at last follow-up. The cost of transvaginal VVF repair is significantly lower compared to repair by minimally invasive approach. Conclusion: Transvaginal VVF repair is comparable to minimally invasive approach in terms of post-operative outcomes and morbidity; however, transvaginal repair performs better in terms of cost and resource utilization.

Immunohistochemistry on cell blocks for diagnosis of malignancy in abdomino-pelvic lesions and ascitic fluid cytology at a rural cancer center: A paradigm shift in cancer management.

Background: Cell block preparation is routine practice in cytopathology these days because of its pivotal role in increasing diagnostic yield and ancillary studies. In the present era of personalized medicine in oncology, ancillary techniques such as immunohistochemistry (IHC) and molecular analysis are gaining more importance. Methods: A retrospective study was conducted in the Department of Pathology, over 6 months, which included 144 cases of Fine Needle Aspiration Cytology (FNAC) of abdominopelvic masses and 105 cases of ascitic fluids. Cell blocks and conventional smears were prepared simultaneously in all cases. IHC was applied on cell blocks and analyzed. Results: IHC was performed on cell blocks in 76 cases of FNA and 53 cases of ascitic fluids. Based on IHC, liver lesions (50 cases) were categorized into metastatic carcinomas with a suggested primary site (45.0%), hepatocellular carcinoma (12.2%), neuroendocrine tumors (16.3%), and malignant melanoma (2%). Using MOC-31 and WT-1, ascitic fluid samples were categorized into benign and malignant. Forty-one out of 53 cases of fluids were diagnosed as metastatic adenocarcinomas with the ovary as the most common primary site. Conclusion: A panel of IHC markers, though not specific alone when applied to cell blocks in a careful clinical and morphological context leads to a rapid and accurate diagnosis. This in turn obviates the need for biopsy in severely ill patients. An astute pathologist can provide accurate results with judicious use of IHC on cell blocks and may bring a sigh of relief for many cancer patients by averting the need for biopsy.

A phase II study of neoadjuvant chemotherapy followed by organ preservation in patients with muscle-invasive bladder cancer.

Objective: Conservative approaches in muscle-invasive bladder cancer (MIBC) have been evolved to avoid aggressive surgery, but are limited to elderly, frail, and patients medically unfit for surgery. Our study aimed to assess the response rate of neoadjuvant chemotherapy (NACT) before radiotherapy (RT) in MIBC patients. Methods: Forty patients with urothelial carcinoma of stage T2-T4a, N0, M0 were enrolled between November 2013 and November 2015, and treated with three cycles of NACT with gemcitabine-cisplatin. Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients who achieved complete response (CR) and partial response (PR) >50% were treated with radical RT, and those who had PR <50%, stable disease (SD), and progressive disease (PD) underwent radical cystectomy (RC). Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model. Results: After NACT, 35 (87.5%) patients achieved either PR >50% or CR, and were treated with RT. Five (12.5%) patients who had PR <50%, SD, or PD underwent RC. All patients who received radiation showed CR after 6 weeks. Median follow-up was 43 months (range: 10-66 months) and median overall survival (OS) was not reached. Three-year OS, local control, and disease-free survival were 70.1%, 60.9%, 50.6%, respectively, and 50% of patients preserved their functioning bladder. Three-year OS rate was 88.9% in patients who achieved CR to NACT, 73.1% in patients with PR ≥50% and 40% in patients with PR <50%. Conclusion: NACT followed by RT provides a high probability of local response with bladder preservation in CR patients. Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.

Comparative analyses of paclitaxel/carboplatin with cisplatin/5-fluorouracil-based chemoradiation in locally advanced inoperable upper and middle third esophageal cancer: A randomized prospective pilot study.

Introduction: Chemoradiation therapy (CRT) remains the treatment of choice for inoperable locally advanced esophageal cancer (LAEC). Several CRT regimens are existent in esophageal cancer, but definitive conclusions are lacking. We performed a pilot study to compare treatment outcome, survival, and toxicities in inoperable upper and middle third esophageal cancer patients undergoing CRT using either paclitaxel/carboplatin or cisplatin/5FU based regimen. Methods: Patients were randomised in two arms (arm A and arm B). In Arm A, taxane-based (Paclitaxel+carboplatin) and in arm B non-taxane-based (cisplatin+5FU) doublet chemotherapy drugs were given concurrently with external beam radiation therapy (EBRT). EBRT in two phases up to a total dose of 54 Gy/27#@2Gy/# was given. Response was subsequently assessed using Response evaluation criteria in solid tumors (RECIST v1.1) and toxicities utilizing Common Terminology Criteria for Adverse Events (CTCAE v 4.0). Result: The overall response rate (ORR) in the taxane-based group was higher than the non-taxane-based group, but was not significantly different (p=0.851). Regarding hematological toxicities, anaemia and reduced cell counts were more in the taxane group compared to the non-taxane group while non-hematological toxicities were comparable. Similarly, better survival with late toxicities were seen with taxane-based arm when compared to non-taxane-based arm, though it was not statistically significant. Conclusion: Our pilot analysis highlights the fact that paclitaxel/carboplatin CRT shows better response, survival, and comparable toxicities when compared to cisplatin/5FU, though statistically nonsignificant. Further randomised prospective trials with large sample size are warranted.